Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator

Area of Science:

• Oncology
• Molecular Biology
• Metabolic Research

Background:

• Metabolic reprogramming is crucial for tumor development and progression.
• Targeting cancer cell metabolism offers therapeutic potential.
• PKCδ-selective activator Roy-Bz shows anti-proliferative activity in colon cancer.

Purpose of the Study:

• To investigate Roy-Bz's antitumor activity in colon cancer by examining its effects on glucose metabolism.
• To elucidate the role of PKCδ in regulating tumor cell metabolism.

Main Methods:

• Assessed mitochondrial respiration and electron transfer chain complex activity in HCT116 cells.
• Analyzed expression of key mitochondrial and glycolytic markers.
• Evaluated Roy-Bz effects in colon cancer tumor xenografts.

Main Results:

• Roy-Bz decreased mitochondrial respiration by inhibiting electron transfer chain complexes I/III.
• Roy-Bz reduced glycolysis by downregulating GLUT1, HK2, and MCT4, and upregulating TIGAR.
• Downregulation of mitochondrial markers (COX4, VDAC, TOM20) and upregulation of SCO2 were observed.
• Results were confirmed in vivo using tumor xenografts.

Conclusions:

• Roy-Bz exhibits antitumor potential in colon cancer by interfering with glucose metabolism.
• PKCδ plays a dual role in tumor cell metabolism, inhibiting both mitochondrial respiration and glycolysis.
• Roy-Bz represents a promising therapeutic agent targeting colon cancer metabolism.